Clostridium acetobutylicum is known for nearly 100 years to produce solvents such as butanol, as well as other bulk chemicals. It was previously shown (B. H. Kim, et al 1984) that the metabolism of Clostridium acetobutylicum can be manipulated in favor of n-butanol and ethanol when its [Fe—Fe]-hydrogenase (encoded by the hydA gene) was inhibited by the use of carbon monoxide. In order to use C. acetobutylicum to continuously produce compounds like lactate, 1,3-propanediol, ethanol, butanol, isobutanol, 1, 3-butanediol, acetate, acetone and isopropanol, 3-hydroxy-3-methylbutyrate, isobutene it would be very useful to inactivate the hydA gene to redirect the electron flux from hydrogen to the production of those chemicals. However, all the attempts to inactivate the hydA gene of C. acetobutylicum have been unsuccessful (Cooksley C. M et al, 2012) so far.
The present invention is based on recent finding by the inventors that by simultaneously inactivating the hydA and the thlA genes encoding respectively the main [Fe—Fe]-hydrogenase and the main thiolase, it is possible to get a C. acetobutylicum mutant strain unable to produce hydrogen.